Abstract
Innate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.
Highlights
Viral infection triggers the recognition of pathogen-associated molecular patterns or danger-associated molecular patterns by host pattern recognition receptors (PRRs), including Toll-like receptors, retinoic-acid-inducible gene I-like receptors, and certain DNA sensors
GBP1 repressed the viral genomic transcription by competitively binding to the vesicular stomatitis virus (VSV)-N substituting for the VSV’s phosphoprotein (VSV-P), which was independent of its guanosine triphosphatases (GTPases) and isoprenylation activity [33] (Fig. 1a), while the inhibitory effect of GBP1 on herpes simplex virus type 1 (HSV-1) is still waiting for exploration
Guanylate-binding proteins (GBPs) are implicated in host-virus interactions, which have emerged as potent modulators
Summary
Viral infection triggers the recognition of pathogen-associated molecular patterns or danger-associated molecular patterns by host pattern recognition receptors (PRRs), including Toll-like receptors, retinoic-acid-inducible gene I-like receptors, and certain DNA sensors. *Correspondence: chenhesu@outlook.com; zheng.alan@hotmail.com 1 Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China Full list of author information is available at the end of the article immunity-related GTPases, Guanylate-binding proteins (GBPs), and very large inducible GTPases [9]. A recent study showed that GBP1 exhibited antiviral activity against VSV and herpes simplex virus type 1 (HSV-1) infection [30].
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